Alternative Anticoagulants Research Articles

Should a physician use the Beers criteria when prescribing direct oral anticoagulants to elderly patients?

The Beers Criteria are a tool for optimizing pharmacotherapy in elderly patients, containing information on potentially inappropriate drugs, which is only advisory in nature and is not mandatory for use in Russian Federation. In the updated version of the Beers Criteria from 2023, the expert opinion on rivaroxaban has changed — instead of "use with caution", as stated in the previous document from 2019, the experts now believe that "long-term treatment with rivaroxaban in non-valvular atrial fibrillation (AF) and venous thromboembolic complications (VTE) should be avoided in favor of safer alternative anticoagulants". This statement is based on moderate-quality evidence obtained from observational studies and network meta-analyses, which are significantly inferior to randomized controlled trials and have numerous limitations. The available evidence base for the use of rivaroxaban in elderly patients with AF and VTE and critical comments on the Beers criteria methodology, indicate the recommendations of the American Geriatrics Society experts regarding direct oral anticoagulants (DOAC) should be treated thoughtfully and carefully. When choosing a DOAC in elderly patients with AF or VTE, one should primarily focus on current clinical guidelines mandatory for use in Russian Federation, and on the data of studies that studied the efficacy and safety of specific DOACs in this category of patients. Rivaroxaban is a well-studied anticoagulant in elderly patients with AF and VTE, since its efficacy and safety have been established in RCTs and specially designed multicenter prospective observational studies with a fairly high quality of evidence. Based on this, rivaroxaban is a justified treatment option for elderly and senile patients with AF or VTE.

Heparin-induced thrombocytopenia in extracorporeal membrane oxygenation-supported patients: a systematic review and meta-analysis

BackgroundIn recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used in critically ill patients with respiratory or cardiac failure. Heparin is usually used as anticoagulation therapy during ECMO support. However, heparin-induced thrombocytopenia (HIT) in ECMO-supported patients, which results in considerable morbidity and mortality, has not yet been well described. This meta-analysis and systematic review aimed to thoroughly report the incidence of HIT on ECMO, as well as the characteristics and outcomes of HIT patients.MethodsWe searched the PubMed, Embase, Cochrane Library, and Scopus databases for studies investigating HIT in adult patients supported by ECMO. All studies conforming to the inclusion criteria were screened from 1975 to August 2023. Nineteen studies from a total of 1,625 abstracts were selected. The primary outcomes were the incidence of HIT and suspected HIT.ResultsThe pooled incidence of HIT in ECMO-supported patients was 4.2% (95% CI: 2.7–5.6; 18 studies). A total of 15.9% (95% CI: 9.0-22.8; 12 studies) of patients on ECMO were suspected of having HIT. Enzyme-linked immunosorbent assay (ELISA) is the most commonly used immunoassay. The median optical density (OD) of the ELISA in HIT-confirmed patients ranged from 1.08 to 2.10. In most studies, the serotonin release assay (SRA) was performed as a HIT-confirming test. According to the subgroup analysis, the pooled incidence of HIT in ECMO patients was 2.7% in studies whose diagnostic mode was functional assays, which is significantly lower than the incidence in studies in which the patients were diagnosed by immunoassay (14.5%). Argatroban was most commonly used as an alternative anticoagulation agent after the withdrawal of heparin. Among confirmed HIT patients, 45.5% (95% CI: 28.8–62.6) experienced thrombotic events, while 50.1% (95% CI: 24.9–75.4) experienced bleeding events. Overall, 46.6% (95% CI: 30.4–63.1) of patients on ECMO with HIT died.ConclusionAccording to our study, the pooled incidence of HIT in ECMO-supported patients is 4.2%, and it contributes to adverse outcomes. Inappropriate diagnostic methods can easily lead to misdiagnosis of HIT. Further research and development of diagnostic algorithms and laboratory assays are warranted.

Anti – intercellular adhesion molecule-1(ICAM-1) nanoparticles for damaged endothelium to treat venous thromboembolism

Venous thromboembolism (VTE) is a potentially fatal vascular disease that can be successfully managed to reduce the risk of mortality and impairment. Anticoagulation therapy is frequently recommended for the treatment and prevention of venous thromboembolism. Despite breakthroughs in anticoagulant therapy using parenteral anticoagulant medications and vitamin K antagonists, limits in their usage persist, prompting research into alternative anticoagulants such as factor Xa inhibitors. Of the agents under development, edoxaban shows the most promise due to strong data confirming its therapeutic benefit for VTE. Nanoparticle drug delivery systems (NDDS) are designed technologies that employ nanoparticles to convey therapeutic drugs in a targeted and regulated manner. Intraendothelial transport of therapies in VTE is facilitated by the induction of cell adhesion molecule-mediated endocytosis upon interaction of intercellular adhesion molecule 1 (ICAM-1) on endothelium cells by ICAM-1-targeted carriers. The potential application of NDDS as nanoparticles as anticoagulant agents has been emphasized. There is proof of outstanding efficacy in preventing blood coagulation, dissolving blood clots, and improving in vivo detection of thrombus. These nanoplatforms’ growing evaluations, strong action, enhanced biocompatibility, and lack of problems from excessive bleeding are all positive signs of their possible integration in the clinical treatment of blood coagulation diseases in the future. Additionally, by avoiding biological barriers and enhancing a medication’s therapeutic index, NDDSs offer superior drug delivery to targeted treatment or even directly to the injured site as compared to standard anticoagulants. Emerging scientific and clinical data suggests that NDDS may be a safe, efficacious, and attractive treatment option for a variety of cardiovascular disorders, including thromboembolic syndromes. This study presents an updated knowledge of nanocarriers for thrombosis as well as an outline of recent significant breakthroughs in targeted thrombosis therapy.

Efficacy and safety of DOACs versus LMWH for elderly patients with active cancer: A meta-analysis.

e13776 Background: Anticoagulant treatment in patients with cancer aims to reduce the high risk of thromboembolism. Direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) are currently approved for the treatment of cancer-related thrombosis. However, there is limited data comparing the efficacy and safety of these two antithrombotic therapies among elderly patients with cancer. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were systematically searched for studies comparing DOACs with LMWH in cancer patients with newly diagnosed venous thromboembolism (VTE) or pulmonary embolism (PE). Both solid tumors and hematologic malignancies were included. Outcomes of interest were recurrent VTE and major bleeding. Odds ratio (OR) with 95% confidence intervals (CI) were pooled with a random-effects model. Statistical analysis was performed with Review Manager 5.4.1. Heterogeneity was assessed using the I2 statistic and chi-squared test. Results: Four studies, three randomized controlled trials (RCTs) and one observational, were included. A total of 3,266 patients older than 65 years who underwent anticoagulation with DOACs (35%) or LMWH (65%) were incorporated in the analysis. There was no statistically significant difference between anticoagulation therapies for recurrent VTE (OR, 0.68; 95% CI, 0.41-1.11; p = 0.13; I² = 56%; Table) or major bleeding (OR, 1.18; 95% CI, 0.61-2.25; p = 0.08; I² = 60%; Table). Conclusions: Our findings suggest no statistically significant differences in recurrent VTE or major bleeding between DOACs and LMWH in elderly oncologic patients with newly diagnosed VTE or PE. Given the practical challenges of using LMWH, DOACs may be considered an alternative anticoagulation strategy for these patients. [Table: see text]

Is There an Alternative Oral Anticoagulation to Vitamin-K-Antagonists for Patients with Mechanical Aortic Valve Replacement? - A Literature Review.

Current guidelines exclusively recommend vitamin-K-antagonists (VKA) as anticoagulation for patients after mechanical aortic valve replacement due to the increased postoperative risk of valve thrombosis and thrombo-embolism. Strict and regular assessments are mandatory during VKA therapy to ensure a potent anticoagulatory effect within the desired range. From the patients' perspective, VKA are associated with relevant interactions and side effects reducing the quality of life and contributing to a high number of patients not achieving the optimal therapeutic target. Direct oral anticoagulants (DOAC) have replaced VKA therapy in the past for several indications, e.g., atrial fibrillation. However, it is still unclear if DOACs could replace VKA therapy in patients after mechanical aortic valve replacement. While the PROACT-Xa study did not show a sufficient anticoagulatory effect of apixaban plus aspirin compared to VKA therapy in patients after mechanical aortic valve replacement, the direct thrombin inhibitor dabigatran and the oral factor Xa inhibitors apixaban and rivaroxaban showed promising results in comparable patient cohorts in smaller studies and case reports. Factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients after mechanical aortic valve replacement. Therefore, factor Xa inhibitors or factor XI inhibitors could provide a potent alternative to VKA for patients after a mechanical aortic valve replacement.

Author Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Author Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Editors' Note: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Editors' Note: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Reader Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Reader Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Use of Andexanet Alfa for Factor Xa Inhibitor Reversal in US Verified Trauma Centers: A National Survey.

Direct oral factor Xa inhibitors are replacing vitamin K-dependent antagonists as anticoagulation treatment in many clinical scenarios. Trauma centers are noting an increase in patients presenting on these medications. The 2018 Food and Drug Administration approval of andexanet alfa provides an alternative anticoagulation reversal. Barriers may limit utilization of new medications including a lack of grade 1A evidence supporting the use of prothrombin complex concentrate (PCC) versus andexanet alfa and cost. To evaluate barriers of andexanet alfa utilization by trauma surgeons, a 15-question survey was conducted. There was a 9% completion rate (n = 89). The results revealed 23.5% would choose andexanet alfa as first-line treatment in children, and 25.8% as first-line treatment in adults. The majority of respondents, 64.7% and 67.4%, would use PCC preferentially in children and adults, respectively. Respondents indicated that cost burden was an overriding factor (76.3%); 42.4% cited lack of high-level efficacy data of andexanet alfa for reversal of factor Xa inhibitors. Additional double-blinded multi-institutional randomized controlled trials comparing 4F-PCC and andexanet alfa for factor Xa inhibitor reversal are needed to support efficacy especially with the increased cost associated.

Effect of Garlic Filtrate as An Alternative Anticoagulant for Osmotic Fragility Test (OFT)

Osmotic fragility test (OFT) is an examination conducted to measure the resistance of erythrocytes when exposed to hypotonic saline solutions with various concentrations. The purpose of this study was to analyze the effect of garlic filtrate as an alternative anticoagulant for osmotic fragility test (OFT). The samples used were blood samples with heparin anticoagulant. This study is a pre-experimental study, using NaCl solution with concentrations of 0.2%, 0.3%, 0.35%, and 0.55%. The method used to measure OFT value is spectrophotometric method. The data obtained were analyzed using statistical one way Anova. The results showed the percentage value of hemolysis with garlic filtrate at each concentration was 100%, 99%, 95%, and 5%, respectively. Data analysis using ANOVA showed that there was a significant effect on the effect of garlic filtrate as an alternative anticoagulant on OFT with (p < 0.05) 0.000 < 0.05.

Evaluating the effectiveness of pseudothrombocytopenia (PTCP) panel with alternative anticoagulants on clinically suspicious EDTA-dependent PTCP: a single tertiary hospital experience

Abstract EDTA is considered the most common anticoagulant to induce pseudothrombocytopenia (PTCP). PTCP panel with alternative anticoagulants (heparin and citrate) has been ordered by clinicians in our hospital for suspicious EDTA-dependent PTCP cases to obtain the correct platelet count (PC). In this study, we aimed to evaluate the effectiveness of alternative anticoagulants on clinically suspicious EDTA-PTCP. We retrospectively identified cases for which PTCP panel (EDTA, heparin, and citrate) was performed from June 2021 to March 2022 using the SAP business intelligence tool. PC was considered significantly different when the difference is more than 25% comparing heparin or citrate to EDTA tubes. Representative cases were chosen for chart review and/or peripheral blood smear review. 200 cases were included in the study. 76 cases had similar PCs in all 3 tubes which represent either true thrombocytopenia or PTCP in all 3 tubes. 17 cases had higher PC on heparin and/or citrate than EDTA which are EDTA-PTCP corrected by alternative anticoagulants (confirmed by smear review). Among those 17 cases: 6/17 had high PC on citrate only, 2/17 on heparin only and 9/17 had higher PC on citrate/heparin. 82 cases had lower PC on heparin only compared to EDTA and 62/82 had heparin exposure. There was 1 case with lower PC on citrate only (no heparin tube) compared to EDTA. 24 cases had lower PC in both heparin and citrate than EDTA tubes (lowest PC on Heparin) and 21/24 have heparin exposure. Peripheral blood smears were reviewed in 39 representative cases. Platelet clumps were identified in the corresponding tubes of all cases. Our study shows that heparin-PTCP is common in hospitalized patients and confirms that heparin is not a suitable alternative anticoagulant for EDTA-PTCP as shown by previous literature. However, many laboratories still use it for EDTA-PTCP. Heparin is known to promote platelet activation which may cause PTCP. The low PC in the heparin tube also seems to be associated with prior heparin exposure. Citrate is a better alternative to EDTA-PTCP. Among cases with low PCs on citrate, nearly all have low PCs on heparin as well. It is interesting to note those cases usually have lower PCs on heparin versus citrate and have prior exposure to heparin. The low PCs on citrate might be partially due to insufficient correction (110%) of PC by the dilution factor of the anticoagulant. Literature showed that a higher corrective factor of PCs is required for citrate. Therefore, a correlation study of PCs in EDTA versus citrate in each lab is needed to establish the corrective factor. Furthermore, delayed processing might be contributing as PCs on citrate are less stable and must be processed within 3 hours.

Anticoagulation management in patients tested for heparin-induced thrombocytopenia in the cardiothoracic intensive care unit diverges from expert guidelines

Abstract Heparin-induced thrombocytopenia (HIT) is a rare, life-threatening complication in patients receiving heparin products. Clinical scoring tools, such as the ‘4T’ score, aim to help identify patients at risk for HIT and are recommended by expert guidelines. For example, the American Society of Hematology (ASH) recommends that patients with an intermediate or high-risk 4T score are presumptively treated for HIT by withdrawing heparin and starting an alternative anticoagulant. At our institution, laboratory HIT testing involves an in-house latex immunoassay (LIA) that, if positive, reflexes to a send-out serotonin release assay (SRA) at the Blood Center of Wisconsin. This confirmation may take several days to result, underscoring the importance of presumptive treatment. Anecdotally, we have observed that clinicians have expressed reservations about the use of the 4T score in the cardiothoracic intensive care unit (CTICU). These reservations may lead to increased HIT testing in patients with low 4T scores and delays in the initiation of alternative anticoagulants. We set out to objectively determine if clinical practice in the CTICU is aligned with ASH guidelines. To do so, we used anticoagulant usage as a proxy for medical decisions made at the time of order for HIT laboratory testing. Data was extracted from the electronic medical records of all patients who were admitted to the CTICU between 5/2018 and 7/2022 and administered a heparin product (n = 1,602). Patients that were not tested for HIT (n = 1,449) were excluded. The remaining patients’ (n = 153) medication record timings were normalized such that the time of their first LIA was set to zero to allow for relative comparisons. 25 (16%) of the LIAs were positive, of which 5 (20%) were confirmed by SRA. Of the 153 patients, 136 (89%) received heparin within 24 hours prior to LIA order, while 6 (4%) were already on alternative anticoagulation (bivalirudin). Of the patients on heparin prior to LIA, 18 (13%) were switched to bivalirudin upon LIA order, 66 (49%) had heparin discontinued without an alternative, and 52 (39%) were continued on heparin. Our results suggest that the prevalence of HIT in this cohort is 3.3% by SRA, much lower than the expected pretest probability estimated for intermediate- and high-risk 4T scores in published meta-analyses. In addition, the observed anticoagulation practices varied widely and diverged from ASH guidelines, where only 17% of patients were on alternative anticoagulation when the testing was ordered. Future work will investigate these patterns across LIA positivity and 4T scores while attempting to address the clinical outcomes of these treatment decisions.

Reader Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Reader Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Author Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Author Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Editors' Note: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Editors' Note: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Anti-factor Xa as the preferred assay to monitor heparin for the treatment of pulmonary embolism.

The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

Quality improvement approaches to heparin-induced thrombocytopenia: a scoping review

BackgroundHeparin-induced thrombocytopenia (HIT) is a relatively uncommon condition characterized by 2 exceedingly common phenomena in hospitalized patients: thrombocytopenia and heparin exposure. Consequently, HIT is frequently overdiagnosed and inappropriately treated. These issues are the focus of many quality improvement (QI) initiatives. ObjectivesIn this scoping review, we identified and characterized all published QI studies on improving the diagnosis and management of HIT. MethodsWe conducted a systematic literature search through April 2022 for studies reporting on QI interventions regarding the diagnosis, treatment, and/or prevention of HIT. ResultsThirty studies were included in the final review. Studies were separated into 5 groups based on the focus of the interventions: increasing HIT recognition, reducing HIT incidence, reducing HIT overdiagnosis, promoting safer HIT management, and creating HIT task forces. Nine studies focused on the implementation of 4Ts score calculator into electronic medical record orders for HIT testing, while only 1 evaluated the impact of reducing unfractionated heparin use in favor of low-molecular-weight heparin. Six studies focused on the implementation of direct thrombin inhibitor management protocols, while none evaluated the use of alternative anticoagulants in HIT management. ConclusionThe bulk of published HIT QI research focused on reducing overdiagnosis and promoting safer direct thrombin inhibitor therapy, while minimal attention has been devoted to HIT prevention and the use of evidence-based alternative HIT therapies.

Anticoagulants in adult extracorporeal membrane oxygenation: alternatives to standardized anticoagulation with unfractionated heparin.

Extracorporeal membrane oxygenation (ECMO) is a vital technique for severe respiratory or heart failure patients. Bleeding and thrombotic events are common during ECMO and negatively impact patient outcomes. Unfractionated heparin is the primary anticoagulant, but its adverse effects limit its use, necessitating alternative anticoagulants. Review available alternative anticoagulants for adult ECMO patients. Explore potential novel anticoagulants for future ECMO use. Aim to reduce complications (bleeding and thrombosis) and improve safety and efficacy for critically ill ECMO patients. Comprehensive literature review of existing and emerging anticoagulants for ECMO. Identified a range of alternative anticoagulants beyond unfractionated heparin. Evaluated their potential utility in mitigating ECMO-related complications. Diverse anticoagulant options are available and under investigation for ECMO. These alternatives may enhance patient safety and outcomes during ECMO support. Further research and clinical studies are warranted to determine their effectiveness and safety profiles.

Heparin-induced thrombocytopenia associated with low-molecular-weight heparin: clinical feature analysis of cases and pharmacovigilance assessment of the FAERS database.

Background: Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are commonly used anticoagulants for the management of arterial and venous thromboses. However, it is crucial to be aware that LMWH can, in rare cases, lead to a dangerous complication known as heparin-induced thrombocytopenia (HIT). The objective of this study was to evaluate the pharmacovigilance and clinical features of HIT associated with LMWH, as well as identify treatment strategies and risk factors to facilitate prompt management. Methods: We extracted adverse event report data from the FDA Adverse Event Reporting System (FAERS) database for pharmacovigilance assessment. Case reports on LMWH-induced thrombocytopenia dated up to 20 March 2023 were collected for retrospective analysis. Results: Significantly elevated reporting rates of HIT were shown in adverse event (AE) data of LMWHs in the FAERS database, while tinzaparin had a higher proportional reporting ratio (PRR) and reporting odds ratio (ROR) than other LMWHs, indicating a greater likelihood of HIT. Case report analysis indicated that a total of 43 patients showed evidence of LMWH-induced thrombocytopenia with a median onset time of 8days. Almost half of the events were caused by enoxaparin. LMWHs were mainly prescribed for the treatment of embolism and thromboprophylaxis of joint operation. Patients with a history of diabetes or surgery appeared to be more susceptible to HIT. Clinical symptoms were mostly presented as thrombus, skin lesion, and dyspnea. Almost 90% of the patients experienced a platelet reduction of more than 50% and had a Warkentin 4T score of more than 6, indicating a high likelihood of HIT. In all patients, LMWHs that were determined to be the cause were promptly withdrawn. Following the discontinuation of LMWHs, almost all patients were given alternative anticoagulants and eventually achieved recovery. Conclusion: LMWH-induced thrombocytopenia is rare but serious, with increased risk in patients with diabetes or a surgical history. Prompt recognition and management are crucial for the safe use of LMWHs.

Alternative anticoagulation during extracorporeal detoxification

The role of heparin anticoagulation in the development of hemorrhagic syndrome after extracorporeal detoxification (ECD) procedures in patients with initial hemostasis disorders, as well as the place of alternative citrate anticoagulation in extracorporeal treatment have not yet received a final assessment and require further study. The aim of this work was to compare the results of treatment of patients with severe intoxication using heparin and citrate as anticoagulants during ECD procedures. The conducted study confirms that the use of heparin anticoagulation in ECD leads to a spasmodic progression of the manifestations of DIC that were present before the procedure. Citrate anticoagulation demonstrates the benefits consisting in the absence of a spasmodic increase in coagulopathy, hypofibrinemia, and thrombocytopenia during an ECD session, which is characteristic of the heparin use. However, when ECD is initiated against the background of more severe initial coagulopathy and, interrelatedly, more severe multiple organ failure (MOF), this does not improve treatment outcomes. Moreover, among patients with severe MOF taken for ECD, there was a greater mortality rate and a large proportion of deaths during and immediately after the session when using citrate anticoagulation. Thus, ECD procedures with citrate anticoagulation may have a negative impact on the condition of patients who already have severe MOF and severe coagulopathy. This risk may be associated with metabolic disorders, especially dangerous in such severe patients, and does not outweigh the risk of an increase in hemostasis disorders characteristic of heparin anticoagulation. Probably, ECD with citrate anticoagulation has to be carried out at an earlier stage of the disease, and in cases of severe MOF already present in the patient, it is advisable to use traditional heparin anticoagulation.